Camptothecin and some of its analogous compounds such as, for example, 9-amino camptothecin, display potent antitumor activity by the inhibition of Topoisomerase I which is a monomeric enzyme involved in some important cellular functions and cellular growth (see, for instance, Wani et al., J. Med. Chem. 1987, 30, 1774; Hsiang et al., Cancer Res. 1989, 49, 4385 and Cancer Res. 1989, 49, 1465).
Unfortunately, camptothecin and some of its derivatives such as the above mentioned 9-amino camptothecin, suffer of low solubility in aqueous solutions. This drawback makes very difficult their administration and the preparation of acceptable pharmaceutical formulations containing them (see, for instance, W. J. Slichenmyer et al., Journal of the National Cancer Institute, Vol. 85, No. 4, 1993, pp 271-291 and, in particular, page 275 for 9-amino camptothecin).
Therefore, there is a need to find new camptothecin derivatives that, while maintaining or increasing biological activity of camptothecin are, in the same time, endowed with water solubility and/or chemicophysical characteristics which make these derivatives suitable for being included in pharmaceutically acceptable formulations.
The compounds of this invention fulfill such a need.